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NEW YORK —The U.S. Open was denied a Roger Federer–Rafael Nadal match yet again. Juan Martin del Potro wasn’t having any of it, just like in 2009.

The Argentine bounced Federer 7-5, 3-6, 7-6 (8), 6-4 in the quarterfinals on Wednesday night, handing the Swiss his first loss in a Grand Slam since the 2016 Wimbledon semifinals.

It also meant that, for the sixth time, Federer and Nadal missed the first U.S. Open meeting of their storied rivalry by a single match.

Del Potro’s play under the Arthur Ashe Stadium roof brought back memories of 2009, when he routed Nadal in the semifinals and came back to overpower Federer in the final to win his first and (for now) only Grand Slam title before four wrist surgeries set back a promising career.

Federer had a pair of double faults on Del Potro’s first two break points, and the mistakes piled as midnight beckoned. Federer said that in two weeks in New York, he didn’t once play with the feeling of the Australian Open in January and Wimbledon in July, when he won his first Slams in five years to reach 19 for his career.

“If I ran into a good guy, I was going to lose, I felt,” he said. “I don’t want to say I was in negative mindset, but I knew going in that I’m not in a safe place. Might have depended too much on my opponent, and I don’t like that feeling. I had it, you know, throughout the tournament, and I just felt that way every single match I went into.”

“He will have a better chance to beat Rafa, to be honest,” Federer said. “The way I played or playing right now, it’s not good enough in my opinion to win this tournament.”

In the women’s bracket, it’s an all-American final four at a Slam for the first time since 1985 Wimbledon and the first time at the U.S. Open since 1981.

Venus Williams will play Sloane Stephens in one Thursday semi, while Madison Keys gets CoCo Vandweghe in the other.

But the anticipation since the draw release two weeks ago was for a semi between Federer and Nadal, the icons having resurgent seasons.

In the middle of the Federer-Del Potro match, the cheapest StubHub men’s semis ticket price was $745, more than twice as much as a men’s final ticket and 10 times the cost of a women’s semis pass.

“I honestly was only thinking about tonight,” Federer said. “My head didn’t even wander during the match.”

Federer and Nadal have played 37 times (Nadal leads 23-14), including 12 at Grand Slams, but never at the U.S. Open (or the Olympics). They were also one match away from meeting in New York in 2008, 2009, 2010, 2011 and 2013.

“It’s something a little bit strange that we never played here, no?” Nadal said on ESPN, after his match and before Federer’s. “I think it will be much more special if that can happen in a final, but it’s not possible this year. We’re going to try to come back and make that happen.”

They’ve combined for 34 Grand Slam singles titles, but bagged none for nearly three years until Federer beat Nadal in the Australian Open final in January.

Nadal won his 10th French Open in June. Federer captured his eighth Wimbledon in July. They are fighting for the year-end No. 1 ranking, boosted in part by season-ending injuries to Novak Djokovic and Andy Murray.

“In some ways I’m actually happy I made the quarters, so I’m not disappointed, because it’s been a good run this year already,” Federer said. “It’s all a bonus at this stage.”

Nadal was pressed to wax poetic on his rivalry with Federer, or just about the Swiss himself, in a news conference after Wednesday’s mismatch.

“I don’t want to look like I gonna be his boyfriend, no?” Nadal joked.

The other semifinal pits two first-timers — South African Kevin Anderson and Spain’s Pablo Carreño Busta — who would be clear underdogs to Nadal or Del Potro in Sunday’s final.

Federer, a 36-year-old with five U.S. Open titles, was forced to five sets in his first two matches last week while fighting off a pre-event back injury. Federer swept his last two opponents before Del Potro but is tired.

“When I walked off the court, I was, like, finally, I can rest,” he said. “Because I’m tired. I put a lot into it. I was not sure I could play, to be honest, so I’m happy I get a rest now.”

Nadal, a 31-year-old with two U.S. Open titles, has dropped two sets in five matches, all against men ranked outside the top 50.

Now he gets Del Potro, a man ranked No. 28 but with the game of a top-10er. The big Argentine isn’t sure what he has left after overcoming illness to win a five-setter in the fourth round and coming from behind to take out Federer.

“Playing against Rafa in my favorite tournament, I will try to enjoy the atmosphere, the game, and I know if I play my best tennis, I could be a danger for him,” he said.